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OBJECTIVES: Tranexamic acid is proposed as a treatment for gastrointestinal bleeding. The Haemorrhage Alleviation with Tranexamic Acid-Intestinal System trial evaluated extended-use (24 hr) high-dose tranexamic acid, prompting a reappraisal for tranexamic acid in gastrointestinal bleeding.
DATA SOURCES: We conducted a systematic review and meta-analysis of randomized controlled trials comparing tranexamic acid with usual care or placebo in adults with gastrointestinal bleeding. We searched MEDLINE, EMBASE, and CENTRAL (inception to September 2019).
DATA SELECTION: Two reviewers independently screened citations, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool in duplicate. The main outcomes were mortality, bleeding, and adverse events.
DATA EXTRACTION: Studies were analyzed as high-dose IV tranexamic acid versus all other dosing strategies for tranexamic acid using fixed-effects models. We assessed certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach.
DATA SYNTHESIS: Five randomized controlled trials evaluated extended-use high-dose IV tranexamic acid, seven evaluating low-dose IV or enteral tranexamic acid. Extended-use high-dose IV tranexamic acid did not reduce mortality (relative risk, 0.98%; 95% CI, 0.88-1.09; I2 = 63%; high certainty) or bleeding (relative risk, 0.92; 95% CI, 0.82-1.04; p = 0.17 and absolute risk differences, -0.7%; 95% CI, -1.5 to 0.3; high certainty) but resulted in a small increase in deep venous thrombosis (relative risk, 2.01; 95% CI, 1.08-3.72; I2 = 0%), pulmonary embolism (relative risk, 1.78; 95% CI, 1.06-3.0; I2 = 0%), and seizure (relative risk, 1.73; 95% CI, 1.03-2.93) with high certainty. Low-dose IV/enteral tranexamic acid did not reduce mortality (relative risk, 0.62; 95% CI, 0.36-1.09; I2 = 0%) but did reduce risk of rebleeding (relative risk, 0.5; 95% CI, 0.33-0.75; I2 = 9%) and need for surgery (relative risk, 0.58; 95% CI, 0.38-0.88; I2 = 11%), with moderate certainty.
CONCLUSIONS: Extended-use high-dose IV tranexamic acid does not improve mortality or bleeding outcomes and increases adverse events. Low-dose/enteral tranexamic acid may be effective in reducing hemorrhage; more evidence is required to demonstrate its safety.
This drug isn't used in used in clinical practice.
I inferred from the text that the addition of the large HALT-IT trial added heterogeneity and canceled out any benefit seen in earlier meta-analyses, but the Forest plots were not published in the paper and the supplemental material was not available at the Critical Care Medicine website. In the absence of a comparative table showing the various differences in all of these trials, it was difficult to put the findings into context. Nonetheless, given the information that we have to date, high-dose tranexamic acid does not appear to be warranted in GI bleeding.
This systematic review evaluates the potential utility of tranexamic acid treatment in gastrointestinal bleeding. While used at high doses did not obtain any benefit (rather it increased the risk of thromboembolic adverse events), low doses could show some potential benefit that deserves further investigation. The results of gastrointestinal bleeding are widely variable according to its origin and location. So a subgroup analysis could have shed more light on the potential differential effects of tranexamic acid in different types of digestive bleeding.
First, this paper is well written with solid methodology and findings consistent with other studies. The question is: Why is this still being evaluated? Although not in my wheel-house, TXA for GI hemorrhage (at whatever dose) has not been shown to provide clinical benefit (Cochrane 2014, NNT Aug 1, 2019, Roberts et al 2020), and may result in a small net increase in harm - VTE (Roberts et al 2020). Less time on TXA inquiry, more time on endoscopy for definitive treatment.